The proteasomes of cells regulate apoptosis (a natural form of cell death for abnormal cells.) Proteasome activity is increased in cancer cells. Proteasome inhibition arrests cell growth and induces apoptosis in abnormal cells. Proteasome inhibition is seen as a useful therapy against cancers such as multiple myeloma and non-Hodgkin’s lymphoma. Because of the toxicity of pharmaceutical proteasome inhibitors, there is great interest in the proteasome inhibition activity of nontoxic dietary flavonoids.

The three main activities of the proteasome are chymotrypsin-like activity (CT-L), trypsin-like activity (T-L) and a peptide hydrolyzing activity. Genestein inhibits the CT-L. Bortezomib (an anticancer drug) and epigallo-catechin 3-gallate (EGCG, from green tea), inhibit peptide hydrolyzation and CT-L.

Flavonoids are polyphenol chemicals found in many plants, wine, tea and coffee. Flavonoid activities are antioxidant, antitumor, antiviral and anti-inflammatory. The strength of a proteasome inhibitor depends on its’ chemical structure. Luteolin, apigenin and chrysin are flavonoids which have been found to inhibit CT-L activity. The activity of these three flavonoids was studied by the authors on cultures of cancer cell lines of liver cancer, lung cancer, leukemia and colon cancer.

The authors found cell death induction to be strongest in the luteolin treated cells. Apigenin was less strong and chrysin was the weakest of the three flavonoids studied. The cell death was found to be due to apoptosis.

CONCLUSION: The authors found that chrysin, apigenin and luteolin inhibited CT-L and T-L catalytic activities of the chromosome. They should be useful to increase apoptosis in treatment of cancer.

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